Authors: Carlos E. Marroquin and a team of researchers from the Dept of Surgery, Division of Transplant and Hepatobiliary Surgery, Georgetown University Medical Center, Washington DC; and the United Network for Organ Sharing, Richmond, Va.

Abstract

A significant number of patients with end-stage liver disease secondary to hepatitis C die of disease-related complications. Liver transplantation offers the only effective alternative. Unfortunately, organ demand exceeds supply. Consequently, some transplant centers have used hepatitis C virus­positive (HCV+) donor livers for HCV+ recipients. This study reviews the clinical outcome of a large series of HCV+ recipients of HCV+ liver allografts and compares their course with that of HCV+ recipients of HCV-negative (HCV­) allografts. The United Network for Organ Sharing Scientific Registry was reviewed for the period from April 1, 1994, to June 30, 1997. All HCV+ transplant recipients were analyzed. Two groups were identified: a group of HCV+ recipients of HCV+ donor livers (n = 96), and a group of HCV+ recipients of HCV­ donor livers (n = 2,827). A multivariate logistic regression model was used to determine the odds of graft failure and patient mortality, and unadjusted graft and patient survival were determined using the Kaplan-Meier method. There were no differences in demographic criteria between the groups. A greater percentage of patients with hepatocellular carcinoma received an HCV+ allograft (8.3% v 3.1%; P = .01). Patient survival showed a significant difference for the HCV+ group compared with the HCV­ group (90% v 77%; P = .01). Blood type group A, group B, group O incompatibility was significant, with 4.2% incompatibility in the HCV+ group and only 1.3% in the HCV­ group (P = .04). Donor hepatitis C status does not impact on graft or patient survival after liver transplantation for HCV+ recipients. Their survival was equivalent, if not better, compared with the control group. Using HCV+ donor livers for transplantation in HCV+ recipients safely and effectively expands the organ donor pool. (Liver Transpl September 2001;7:762-768.)

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Approximately 4 million Americans are infected with hepatitis C virus (HCV). During their lifetime, an estimated 20% of HCV-infected individuals will develop cirrhosis and subsequently develop complications of cirrhosis, including ascites, encephalopathy, and/or variceal bleeding. A significant number of these individuals will eventually die of disease-related complications. For some, if not most, of these individuals, liver transplantation offers the only truly effective alternative. Unfortunately, the demand for liver transplants far exceeds the organ supply. Given the prevalence of HCV infection in the population, approximately 2% to 5% of potential organ donors are also infected with HCV. Because of concerns about viral transmission and allograft dysfunction, these organs were not generally considered for use in transplantation, potentially wasting viable organs.

Given the significant disparity between organ supply and demand for transplantation, it becomes critical to develop new technologies to support patients with end-stage liver disease. In the absence of new means of support, it is crucial to consider ways to expand the viable organ supply. Some groups have turned toward using marginal donors for liver transplantation, with reasonable success. Specifically, Fishbein et al found that livers with severe microvesicular steatosis can be used for transplantation with 1-year patient and graft survival rates of 80% and 72%, respectively. Furthermore, Mor et al found that extending their limits to accept older donors and those with moderately abnormal liver function test results or prolonged ischemic times did not affect graft survival.

However, even the incorporation of marginal organs into the donor pool leaves a huge deficit in the necessary supply. Therefore, other groups have used hepatic allografts from HCV+ donors for transplantation into HCV+ recipients. One concern regarding the use of HCV+ donor livers for transplantation is that one might introduce a more virulent strain of virus than the patient already harbors. However, there is little evidence to support this concern. Vargas et al showed that transplant recipients in whom the predominant HCV genotype belonged to the donor were less likely to develop recurrent hepatitis than those patients who retained their original strain. Because these studies were from single Institutions, we sought to confirm these findings on a larger national scale using the UNOS SR.

One alternative is to transplant HCV-positive (HCV+) donor livers into HCV+ patients with end-stage liver disease. Some groups have found this to be a safe and effective practice. Vargas et al3 found no significant difference in 1- and 5-year survival of patients who received an HCV+ donor liver compared with those who received an HCV-negative (HCV­) donor liver. Furthermore, there was no difference in graft failure rates between the 2 groups. Moreover, when they examined the risk for infection with donor viral strain, they found that patients in whom the predominant HCV genotype after transplantation was that of the donor were significantly less likely to develop recurrent hepatitis than those patients who retained their own strain. Similarly, Testa et al found no difference in patient and graft survival when they compared their institution's experience with recipients of an HCV+ donor liver versus recipients of an HCV­ donor liver.

Previous reports examining the use of HCV+ allografts have been hindered by small study populations. The purpose of this study is to compare clinical outcomes of a large series of HCV+ recipients of liver allografts from either HCV+ or HCV­ donors using the United Network for Organ Sharing (UNOS) Scientific Registry (SR). UNOS coordinates the 272 transplant centers and the medical, scientific, and technological resources needed to facilitate organ transplantation nationally. The UNOS SR provided the large numbers necessary to overcome the small sample size hindering other studies. The goal is to determine the effect of hepatitis C serology of the donor on patient and graft survival. Other factors that were compared included recipient and donor characteristics, effect of coexisting diseases, liver function test, immunosuppression, UNOS status at transplantation, and causes of graft failure. Finally, the most important goal is to establish whether one could safely expand the donor pool by using livers from HCV+ donors for patients with end-stage liver disease secondary to hepatitis C.

Only 10% (n = 10) of the HCV+ donor group died during the study period versus 23% (n = 633) of the HCV­ donor group. Patient survival rates for the 2 groups at 6, 12, 18, and 24 months were 95%, 90%, 90%, and 90% versus 85%, 82%, 79%, and 77%, respectively. Median follow-ups were 1,023 days for the HCV+ donor group and 1,123 days for the HCV­ donor group. When UNOS status at time of transplantation was reviewed, the comparison of waiting list status was significantly different (Table 5).

A greater percent of status 3 patients received an HCV- graft than status 1 patients (Table 5). This may provide a better explanation for the improved survival. Because these patients received their grafts before they were hospitalized or ICU bound, they had the physiological reserve necessary to translate into an improved outcome.

To safely optimize the use of all available livers for transplantation, the practice of performing biopsies before procurement should be adopted when a question of organ viability arises. If significant steatosis or fibrosis is noted, that allograft should be abandoned. Despite the observed safety of using HCV+ donor livers for transplantation, there will always be concern with the potential risk for greater infectivity and pathogenicity of concurrent infection with 2 different viral strains and a greater rate of viral recurrence. To ameliorate or at least lessen the risk for graft failure secondary to recurrent hepatitis, one strategy may involve posttransplantation antiviral therapy as an adjunct to using HCV+ donor organs.
Johnson et al9 found that antiviral therapy with interferon-alfa significantly improved the clinical course of patients who developed recurrent HCV hepatitis after liver transplantation. Further support for adjuvant therapy is provided by Boillot et al, who found that early and prolonged interferon-alfa therapy improved graft survival. Therefore, similar benefits may be derived from treatment of HCV+ patients who receive an HCV+ donor organ with interferon-alfa.

Although this study only bridges a 2-year period, it is the first large-scale analysis indicating that donor hepatitis C status does not negatively impact on either graft or patient survival after liver transplantation of an HCV+ patient. Greater long-term follow-up is needed to be certain of the safety and efficacy of this practice. However, given the limited number of organs, it is necessary to continue to develop new strategies to optimize the utilization of all available allografts.